a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial to evaluate the safety, tolerability, and efficacy of mk-8457 in participants with rheumatoid arthritis (mk-8457-010)

Conditions: Rheumatoid Arthritis

Summary: the purpose of this study is to assess the safety and efficacy of mk-8457 + methotrexate (mtx) in participants with active rheumatoid arthritis (ra) and an inadequate response or intolerance to anti-tumor necrosis factor α (anti-tnf-α) therapy. the primary hypothesis of this study is that among participants with active ra, mk-8457 100 mg twice daily (bid) + mtx will be superior to placebo + mtx as measured by the change in disease activity score 28 c-reactive protein (das28-crp) after 12 weeks of treatment.

in the base study, participants were to receive blinded mk-8457 100 mg + mtx or matched placebo + mtx for up to 24 weeks. at week 12 and 18, efficacy evaluation was conducted to assess eligibility for early escape, defined as \<20% improvement in tender and swollen joint counts. participants who completed the base study and those eligible for early escape could enroll in the 76-week safety extension in which participants were to receive open-label mk-8457 100 mg bid + mtx. all participants must have been treated with mtx for at least 3 months prior to screening and have been receiving a stable dose of mtx for at least 4 weeks prior to screening. in addition, each participant must have either failed treatment with 1 or 2 anti-tnf-α therapies or was intolerant to anti-tnf-α therapy prior to screening. for participants who failed therapy, the treatment with anti-tnf-α therapies must have been for at least 3 months.

Eligibility criteria:
inclusion criteria: * diagnosis of rheumatoid arthritis for at least 6 months prior to screening * active rheumatoid arthritis as defined by the presence of \>= 6 swollen joints (of 66 count) and \>= 6 tender joints (of 68 joint count) * c-reactive protein blood level \>0.9 mg/dl or an elevated erythrocyte sedimentation rate (esr) \>28 mm/hr and evidence of synovitis on imaging * american college of rheumatology functional class i, ii, or iii * received methotrexate for a minimum of 3 months prior to screening with a regionally appropriate stable weekly dose for at least 4 weeks prior to screening. the dose of methotrexate must remain stable through week 24 of the study. * failed treatment with 1 or 2 anti-tumor necrosis factor alpha (anti-tnf-α) therapies or was intolerant to anti-tnf-α therapy prior to screening * if using non-steroidal anti-inflammatory drugs or other analgesics, participant must be on a stable dose * no history of either untreated latent or active tuberculosis (tb) prior to baseline * participants of reproductive potential must agree to remain abstinent or use 2 acceptable methods of birth control exclusion criteria: * presence of inflammatory disease other than rheumatoid arthritis, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, or lyme disease * hospitalization due to an acute cardiovascular event, cardiovascular illness, or cardiovascular surgery within 6 months of screening * participant has a transplanted organ, excluding corneal transplant, performed \> 3 months prior to the first dose of trial medication * history of, or current ongoing ,chronic or recurrent infectious disease * positive hepatitis b surface antigen or hepatitis c test result * human immunodeficiency virus (hiv) positive * user of recreational or illicit drugs or has had a history (within the previous 2 years) of drug or alcohol abuse or dependence * prior exposure to fostamatinib or other spleen tyrosine kinase inhibitors * prior exposure to 3 or more anti-tnf therapeutic agents * has been treated for ra with a marketed biologic agent (other than anti-tnf therapeutic agents) and failed the agent due to lack of efficacy * currently participating in another interventional clinical trial or has participated in an interventional clinical trial within 4 weeks prior to screening * severe opportunistic infection within the 6 months prior to screening